It has become increasingly apparent that epigenetics, where the genome interacts with the environment, is central to our understanding of the relationship between aging and disease. DNA methylation is a key epigenetic mechanism controlling gene expression. Recent data suggest that there is a considerable epigenetic "drift" in aging, resulting in relative DNA hypomethylation in many tissues including T cells. The original RO1 was funded to examine the effect of aging on the epigenetic control of leukocyte chemokine system. We showed that aging is associated with increased T cell pro-inflammatory chemokine function that is at least in part controlled by DNA methylation. In this competing renewal, we will determine if the aging changes can be ameliorated by altering the T cell epigenome during the critical stages of immune system development. We hypothesize that the prenatal 'epigenetic environment'can modify T cell chemokine receptor response that will in turn determine the late-life susceptibility to chronic inflammatory diseases. Specific Aim 1 will determine the effect of a pre-natal methyl-donor supplementation diet on murine T cell chemokine function throughout the life span. Specific Aim 2 will assess the consequence of diet-induced epigenetic changes on the onset and progression of coronary artery disease. PUBLIC HEALTH RELEVANCE: The mechanistic link between aging and chronic diseases in the elderly is poorly understood. Using mouse models, the proposal will examine the effect of a pre-natal methyl-donor supplementation diet on the onset and progression of coronary artery disease in late life.